Expansion of EBV latent membrane protein 2a specific cytotoxic T cells for the adoptive immunotherapy of EBV latency type 2 malignancies: Influence of recombinant IL12 and IL15

Hans Joachim Wagner, U. Sili, B. Gahn, S. Vigouroux, M. H. Huls, W. Xie, D. Vignali, Malcolm Brenner, Helen Heslop, C. M. Rooney

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Background: EBV-associated malignancies with a Type II latency gene expression pattern, such as EBV-positive HD, or nasopharyngeal carcinoma, frequently express the EBV latency Ag LMP2a. Hence, they provide a potential target for adoptive immunotherapy using in vitro-generated LMP2a-specific cytotoxic T lymphocytes (CTL). In this study, LMP2a-specific CTL mere specifically amplified and the influence of rIL12 and rIL15 on the culture outcome was tested. Methods: PBMC from donors were stimulated twice with autologous DC transduced with an adenovirus vector expressing LMP2a. This led to a significant expansion of LMP2a-tetramer-specific CTL, which were subsequently further expanded with autologous EBV-transformed B-lymphoblastoid cells (LCL). The addition of rIL12 and rIL15 to the standard IL2-containing culture medium enhanced the proliferation of LMP2a-specific CTL. Results: While rIL15 did not change the pattern of cytokines secreted by LMP2a-CTL, rIL12 enhanced the production of Th1/Tc1 cytokines, such as IFN-γ, while suppressing the production of the Th2/Tc2 cytokine IL5. Discussion: Stimulation of CTL cultures with rIL12 or rIL15 will generate CTL more rapidly, facilitating the application of this approach for patients with these EBV-associated disorders.

Original languageEnglish (US)
Pages (from-to)231-240
Number of pages10
JournalCytotherapy
Volume5
Issue number3
DOIs
StatePublished - 2003

Keywords

  • Adenoviral transduction
  • Adoptive immunotherapy
  • Cytotoxic T cells
  • Dendritic
  • Epstein-Barr virus
  • Hodgkin's disease
  • Latent membrane protein (LMP)2a
  • Nasopharyngeal carcinoma

ASJC Scopus subject areas

  • Immunology

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